(Georgia Institute of Technology, 2021-05)
Schroeder, Michelle
Monoclonal antibodies (mAbs) are highly specific antigen binding proteins that are used as biological reagents, therapeutics, and in rapid diagnostics. While mAbs have extensive potential applications, their means production for small molecules and conformationally specific peptides is difficult. Here, we use a method of mAb production in which we pair conjugate virus-like particle (VLP) vaccine with hybridoma technology to produce high-affinity mAbs against three classes of molecules 1) fentanyl derivatives, 2) SARS-CoV-2 peptides, and 3) α-amanitin and microcystin LR cyclic peptide toxins. We successfully produced broad and derivative-selective mAbs against eight fentanyl derivatives. We also showed early signs of success targeting neutralizing and mutant SARS-CoV-2 peptides with conformational specificity using a heterologous prime-boost strategy. Lastly, we produced high affinity mAbs for both α-amanitin and microcystin LR, two highly toxic cyclic peptides. The early success of mAb production against the variety of targets presented in this thesis shows the viability and exceptional versatility of conjugate VLP vaccines as a means to producing mAbs.
(Georgia Institute of Technology, 2019-05)
Guldberg, Sophia
Approximately 1 in 8 women in the United States will be diagnosed with breast cancer. Among these women, 25-30% will have breast cancer where the HER2 gene is overexpressed and human epidermal growth factor receptor 2 (HER2) is overexpressed, which increases the aggressiveness of the cancer. The aggressiveness of HER2-positive breast cancer results in decreased long-term survival. For this reason, new HER-2 targeted therapies need to be developed to increase remission and survival of HER2-postive breast cancer patients. A notable success in this field has been the use of Genentech’s anti-HER2 antibody (Herceptin, trastuzumab), but this is an expensive option that not all patients can access and must still be frequently combined with chemotherapy drugs.
Protein nanoparticles (PNPs) are increasingly used in a wide variety of biotechnology settings due to their low toxicity, high potential specificity deriving from their polyvalent nature, and low cost. This project focuses on the modification of PNPs to target HER2-positive breast cancer cells for drug delivery. The relative success of this project was determined by flow cytometry and fluorescence microscopy, which confirmed the binding of targeted PNPs and a lack of nonspecific binding. While further experimentation in cytotoxicity and in vivo studies is needed, this project presents a novel and successful method of targeting HER2-positive breast cancer cells with PNPs.